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Stakeholder Opinions: Asthma Phenotypes A changing paradigm

DateMar, 2007
Pages178

€3 040 

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Abstract:

Introduction

An estimated 34 million people are diagnosed with asthma in the major markets. The disease can be broken down into various phenotypes, differentiated by severity, trigger, or predominant inflammatory type. These phenotypes may have important consequences for future approaches to treat asthma in a more targeted fashion, doing away with the one-size-fits-all approach.

Scope

Analysis of the main asthma phenotypes and their pathobiological characteristics Overview of the prevalence of the main phenotypes in asthma Assessment of key unmet needs and the opportunities they offer for new product development Analysis of the future role of phenotypes and their impact in drug development

Highlights

Refractory asthma seems to be resistant to corticosteroids, and some refractory patients also suffer from chronic airflow obstruction. Resistant disease is thought to afflict about 10% of asthma patients, whose unmet medical needs are for obvious reasons very high. On average, 60% of the adult asthmatic population suffer from allergic asthma. These patients are often well controlled with an early onset of disease and less severe symptoms compared to the non-allergic phenotype. Immunotherapy is suggested to be beneficial for some of the more severe allergic asthmatics. Two inflammatory phenotypes dominate in asthma: eosinophilic and neutrophilic. These types of inflammation can be seen across a variety of phenotypes, although it is thought that eosinophilic inflammation is mostly associated with allergic asthma and neutrophilic inflammation is associated with refractory asthma and chronic airflow obstruction.

Reasons to Purchase

Evaluate different asthma phenotypes and their prevalence in the seven major markets Explore differential treatment and the unmet needs of the most important asthma phenotypes Appreciate the impact of various phenotypes on the future of drug development for asthma




Table of contents:
 ABOUT DATAMONITOR HEALTHCARE 2
About the Infectious Diseases and Respiratory (ID&R) analysis team 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the report 3
Contributing experts 3
Datamonitor insight into asthma phenotypes 4
CHAPTER 2 ASTHMA BACKGROUND AND EPIDEMIOLOGY 11
Disease definition 11
Causes of asthma: environment and genes 11
Etiology 14
Disease classification and phenotypes 16
Phenotypes 18
Prevalence 21
CHAPTER 3 ASTHMA DIAGNOSIS AND TREATMENT OPTIONS 24
Presentation and diagnosis 24
Treatment options and guidelines 25
Bronchodilators 26
Beta2-agonists 27
Anticholinergics 28
Combination beta2-agonist/anticholinergic 28
Anti-inflammatories 29
Inhaled corticosteroids 29
Systemic corticosteroids 30
Non-steroidal anti-inflammatory drugs (NSAIDs) 30
ICS/LABA combinations 32
Biologicals 33
Future trends in asthma treatment 33
Asthma biomarkers 34
CHAPTER 4 CLINICAL OR PHYSIOLOGICAL PHENOTYPES 38
Severity-defined asthma 38
Prevalence 40
Refractory asthma 42
Pathobiology 44
The refractory asthma patient 46
Prevalence 47
Treatment 48
The exacerbation-prone subtype of refractory asthma 50
Chronic airflow obstruction in asthma 51
Pathobiology 51
The asthma patient with chronic airflow obstruction 54
Prevalence 56
Treatment 59
Asthma defined by age of onset 60
The early- versus late-onset patient 60
Treatment 62
Nocturnal asthma 63
Pathobiology 64
Prevalence 65
Treatment 66
Viral infections during childhood 66
Asthma and obesity 68
CHAPTER 5 PHENOTYPES RELATED TO CERTAIN TRIGGERS 72
Environmental allergens 72
Pathobiology 73
The allergic march 75
The allergic versus non-allergic asthma patient 77
Prevalence 79
Treatment 82
Immunotherapy 82
Aspirin- and NSAID-sensitive asthma 85
The aspirin-sensitive asthma patient 85
Prevalence 86
Treatment 88
Occupational allergens or irritants 89
Prevalence 92
Treatment 93
Menses-related asthma 94
Exercise-induced asthma 95
Treatment 96
CHAPTER 6 INFLAMMATORY PHENOTYPES 98
Eosinophilic inflammatory asthma 99
Prevalence 100
Neutrophilic inflammatory asthma 103
The neutrophilic asthma phenotype 105
Prevalence 106
Pauci-granulocytic inflammatory asthma 108
Prevalence 108
CHAPTER 7 ASTHMA PHENOTYPES IN THE FUTURE 111
Why and how could we use phenotypes? 112
Phenotypes and endpoints 113
New endpoints 114
The battle over asthma control 116
Phenotypes and biomarkers 117
How can we progress the identification of phenotypes? 118
Which phenotype should we target first? 120
Case study 1: Xolair (omalizumab) in severe allergic asthma 125
Case study 2: Immunotherapy in severe allergic asthma 127
Case study 3: an anti-inflammatory drug in neutrophilic asthma 129
REFERENCES 132
Disclaimer 178
List of Tables
Table 1: Asthma prevalence and diagnosed population by country and age, 2007 23
Table 2: Diagnosed asthma by country and severity for children and adults/elderly, 2007 41
Table 3: Prevalence of severe/refractory asthma by country, 2007 47
Table 4: Prevalence of exacerbation-prone severe/refractory asthma by country, 2007 51
Table 5: Prevalence of chronic airflow obstruction in diagnosed adult/elderly and pediatric asthma population by country (000s), 2007 58
Table 6: Prevalence of diagnosed asthma patients with nocturnal symptoms in the seven major markets (million), 2007 65
Table 7: The prevalence of allergic and non-allergic asthma in the seven major markets, 2007 ('000) 80
Table 8: Prevalence of allergic asthma according to severity in the seven major markets, 2007 ('000) 81
Table 9: Range of prevalence of diagnosed asthma patients with aspirin/NSAID sensitive asthma, 2007 88
Table 10: Prevalence of occupational asthma in the diagnosed adult asthma population, 2007 93
Table 11: Prevalence of diagnosed asthma patients with predominantly eosinophilic inflammation, 2007 ('000) 102
Table 12: Prevalence of diagnosed asthma patients with predominantly neutrophilic inflammation, 2007 107
Table 13: Prevalence of different inflammatory phenotypes in diagnosed asthmatic children, adults and elderly, 2007 ('000) 110
Table 14: Marketed and pipeline therapies in eosinophilic and neutrophilic inflammation 125
List of Figures
Figure 1: Basic etiology of asthma 16
Figure 2: Levels of asthma control according to the GINA guidelines 18
Figure 3: Early/childhood onset phenotypes 20
Figure 4: Late/adult onset phenotypes 20
Figure 5: Percentage of asthma patients who experience daily or weekly symptoms by age, 2004 24
Figure 6: Management approach based on asthma control 26
Figure 7: Novel asthma therapies are moving towards targeted therapy 34
Figure 8: The role of biomarkers related to asthma therapy 36
Figure 9: Overview of clinical or physiological phenotypes 38
Figure 10: Classification of asthma by clinical, pretreatment features 39
Figure 11: ATS workshop consensus for definition of refractory asthma 43
Figure 12: A normal airway compared to the process in airway remodeling 53
Figure 13: Early-onset versus late-onset asthma 61
Figure 14: Circadian alterations in lung function in healthy subjects and patients with nocturnal asthma 63
Figure 15: Viral infections have been implicated in at least three ways with asthma pathogenesis 67
Figure 16: Overview of phenotypes related to certain triggers 72
Figure 17: The early and late allergic response 73
Figure 18: Proposed systemic inflammatory mechanisms linking the upper and lower airways 75
Figure 19: The allergic march 77
Figure 20: Prevalence of aspirin-sensitive asthma according to studies versus key opinion leaders (KOLs) 87
Figure 21: Categories and subcategories of occupational asthma 90
Figure 22: Overview of inflammatory phenotypes 98
Figure 23: Characteristics of eosinophil-positive (+) and eosinophil-negative (-) severe asthma 104
Figure 24: The complex relation between various triggers of airway inflammation and the diseases associated with them 111
Figure 25: Exacerbations in patients following guideline-therapy and sputum-identification therapy 113
Figure 26: How can we progress the identification of asthma phenotypes? 119
Figure 27: The reaction of neutrophils to CXC chemokines in the early phase of inflammation 123
Figure 28: The difference between potential US peak sales and actual US sales of Xolair in allergic asthma 127
Figure 29: Possible US peak sales of Grazax in allergic asthma 129
Figure 30: Possible US peak sales of a novel anti-inflammatory in neutrophilic asthma 131




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